FLARE RT for Patients With Stage IIB-IIIB Non-small Cell Lung Cancer: Personalizing Radiation Therapy Using PET/CT and SPECT/CT Imaging

Phase 2

Completed

Conditions: Stage IIB Lung Non-Small Cell Carcinoma AJCC v7
Stage IIIA Lung Non-Small Cell Cancer AJCC v7
Stage IIIB Lung Non-Small Cell Cancer AJCC v7

Interventions: Procedure: Computed Tomography
Radiation: Fludeoxyglucose F-18
Other: Laboratory Biomarker Analysis
Procedure: Positron Emission Tomography
Radiation: Radiation Therapy
Procedure: Single Photon Emission Computed Tomography
Radiation: Technetium Tc-99m Albumin Aggregated
Radiation: Technetium Tc-99m Sulfur Colloid

Registration Number: NCT02773238

Lead Sponsor: University of Washington

Brief Summary: This phase II trial studies how well positron emission tomography (PET)/computed tomography (CT) and single positron emission computed tomography (SPECT)/CT imaging works in improving radiation therapy treatment in patients with stage IIB-IIIB non-small cell lung cancer. PET/CT imaging mid-way through treatment may be able to accurately show how well radiation therapy and chemotherapy are working. SPECT/CT imaging may be able to tell which parts of the lung tissue are healthier than others. Based on the result of the imaging, treatment adjustments may be made to the radiation therapy to improve survival and decrease toxicity.

Detailed Description: OUTLINE: This is a dose-escalation study of radiation therapy.

Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.

After completion of study treatment, patients are followed up for 2 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 51

Inclusion Criteria

Pathologically proven (either histologic or cytologic) diagnosis of stage IIB-IIIB non-small cell lung cancer (NSCLC); according to American Joint Committee on Cancer (AJCC) staging, 7th edition
- Staging workup must include: brain imaging (CT head or magnetic resonance imaging [MRI] brain) and PET/CT
- Pleural effusions must have cytology to rule out malignant involvement unless too small to undergo thoracentesis per radiology
Patients must be considered unresectable or inoperable
Patient must not have received prior radiation for this lung cancer
Patients must be having concurrent chemotherapy
Nodal recurrences can be treated on this protocol but prior curative surgery for lung cancer must have been at least 6 months prior to the nodal recurrence
Patients must have measurable or evaluable disease that is FDG avid with standardized uptake value (SUV) > 3 on PET/CT
Zubrod performance status 0-1
PFTs including forced expiratory volume in 1 second (FEV1) within 26 weeks prior to registration; for FEV1, the best value obtained pre- or post-bronchodilator must be >= 0.8 liters/second or >= 50% predicted
Blood cell count (CBC)/differential obtained within 8 weeks prior to registration on study
Absolute neutrophil count (ANC) >= 1,800 cells/mm^3
Platelets >= 100,000 cells/mm^3
Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable)
Serum creatinine within normal institutional limits or creatinine clearance >= 40 ml/min
Bilirubin must be within or below normal institutional limits
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x the institutional upper limit of normal (IULN)
Patient must sign study specific informed consent prior to study entry

Exclusion Criteria

> 10% unintentional weight loss within the past month
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Laboratory Biomarker Analysis	Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.
Treatment	Positron Emission Tomography	Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.
Treatment	Fludeoxyglucose F-18	Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.
Treatment	Computed Tomography	Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.
Treatment	Radiation Therapy	Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.
Treatment	Single Photon Emission Computed Tomography	Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.
Treatment	Technetium Tc-99m Albumin Aggregated	Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.
Treatment	Technetium Tc-99m Sulfur Colloid	Patients undergo functional avoidance radiation therapy during weeks 1-3. Patients undergo fludeoxyglucose F-18 FDG PET/CT at baseline, 3 weeks, and 3 months post-radiation therapy and undergo technetium Tc-99m albumin aggregated (99mTc-MAA) and technetium Tc-99m sulfur colloid SPECT/CT radiation therapy at baseline and 3 months post-radiation therapy. Baseline PET/CT must be performed at University of Washington Medical Center/Seattle Cancer Care Alliance and be within one month of treatment start, therefore some patients may need to repeat a baseline PET/CT if their PET/CT is from an outside institution or \> 1 month old. Patients not responding to treatment at 3 weeks, will receive an increased daily radiation therapy dosage.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) Rate	At 2 years	Final statistical analyses of OS will consist of Kaplan-Meier estimation.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	1 year	Progression-free survival will be assessed by post-radiotherapy computed tomography. Progression will be defined by RECIST criteria. Final statistical analyses of PFS will consist of Kaplan-Meier estimation.
Change in Pulmonary Function (Diffusing Capacity of the Lungs for Carbon Monoxide [DLCO])	Baseline to 3 months post-radiation therapy	Pulmonary function tests (DLCO, % predicted) will be performed and change over time will be evaluated.
Radiation Pneumonitis Defined as Common Terminology Criteria for Adverse Events Version 4 Grade 2 or Higher Pneumonitis	Up to 3 months	Common Terminology Criteria for Adverse Events version 4, grade 2 or higher pneumonitis is defined as breathing problems after radiation treatment requiring medications for treatment (grade 2), oxygen use (grade 3), hospitalization (grade 4), or leading to death (grade 5). Clinical studies commonly report how many patients that develop pneumonitis as a result of radiation treatment, which is usually within the first 3 months after radiation.
Local-Regional Progression as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria	At 1 year	Intrathoracic progression of lung tumors assessed by post-radiotherapy computed tomography. Progression will be defined by RECIST criteria. Final statistical analyses of local-regional progression cumulative incidence will consist of Fine-Gray estimation with death and distant metastasis as competing risks.
Change in Pulmonary Function-forced Expiratory Volume in 1 Second (FEV1)	Baseline to 3 months post-radiation therapy	Pulmonary function tests (FEV1, liters) will be performed and change over time will be evaluated.

Trial Locations

Locations (2): SCCA Proton Therapy Center
🇺🇸
Seattle, Washington, United States
Fred Hutch/University of Washington Cancer Consortium
🇺🇸
Seattle, Washington, United States